A technique called MS/NTS analysis (tandem mass spectrometry) has been widely used as one of techniques for mass spectrometry, in order to perform identification, structural analysis, or quantitative determination of a high molecular-weight substance. Various configurations have been proposed for mass spectrometers for the MS/MS analysis, and a tandem quadrupole mass spectrometer is normally used because of the simple structure and easy operation and handling.
In the tandem quadrupole mass spectrometer, ions generated from an ion source and originating from a compound are introduced into a front-stage quadrupole mass filter (usually represented as Q1), and ions each having a specific mass-to-charge ratio m/z are sorted out as precursor ions. The precursor ions are introduced into a collision cell in which a quadrupole (or higher multipole) ion guide (usually represented as q2) is housed. Collision-induced dissociation (CID) gas such as argon is supplied into the collision cell, and the precursor ions collide with the CID gas in the collision cell, so that precursor ions are fragmented and various product ions are generated. The product ions are introduced into a rear-stage quadrupole mass filter (usually represented as Q3), and product ions each having a specific mass-to-charge ratio m/z are sorted out and reach a detector to be detected.
An MRM measurement mode is one of MS/MS measurement modes in the tandem quadrupole mass spectrometer. In the MRM measurement mode, fixed mass-to-charge ratios are used for ions that can pass through the front-stage quadrupole mass filter and the rear-stage quadrupole mass filter, and the intensity (amount) of specific product ions corresponding to specific precursor ions is measured. In such MRM measurement, ions originating from non-targeted compounds and foreign components and neutral particles can be removed by the two-stage mass filters, and hence an ion intensity signal having a high SN ratio can be obtained. Accordingly, the MRM measurement is particularly effective for quantitative determination of a slight amount of component and the like.
Such a tandem quadrupole mass spectrometer as described above is used alone in some cases, and is used in combination with a liquid chromatograph (LC) or a gas chromatograph (GC) in many cases. For example, an LC/MS/MS including a tandem quadrupole mass spectrometer as a detector of a liquid chromatograph is frequently used, for example, for quantitative analysis on compounds included in a sample containing a large number of compounds and a sample including foreign substances.
In the case of performing an MRM measurement by the LC/MS/MS (or GC/MS/MS), prior to measurement on a target sample, the combination (hereinafter, referred to as the “MRM transition”) of the mass-to-charge ratio of target precursor ions and the mass-to-charge ratio of target product ions needs to be set as one of measurement conditions, in association with the retention time of each target compound. By setting the MRM transition best suited for each target compound, the signal intensity of ions originating from each target compound can be obtained with high accuracy and sensitivity, and quantitative determination of the target compound can be performed with high accuracy and sensitivity. Although the MRM transition can be manually set by an analysis operator, the manual setting is troublesome, and the best combination cannot necessarily be set.
In view of the above, the MRM transition is conventionally set in the following manner.
First, an analysis operator specifies only the mass-to-charge ratios of precursor ions originating from a target compound. Consequently, product ion scan measurement concerning the specified precursor ions is performed on a known sample containing the target compound, and a predetermined number of product ion peaks are selected in the order of higher signal intensity on a product ion spectrum obtained as a result of the product ion scan measurement. Then, the combination of the precursor ions specified by the analysis operator and product ions corresponding to the selected peaks is defined as the MRM transition.
According to the above-mentioned method, even if the analysis operator does not know the mass-to-charge ratio of target product ions, appropriate product ions are found, and the MRM transition can be automatically set. However, the kind of generated product ions may be different depending on parameters such as the magnitude of collision energy (CE) voltage applied to fragment precursor ions, and product ions generated only under a certain restricted condition may exhibit high signal intensity. Hence, product ions exhibiting low signal intensity may be more suited for quantitative determination than product ions exhibiting high signal intensity. To deal with this, for example, in a proposed method, product ion scan measurement is performed several times, and product ions are selected in the order of larger appearance frequency on each of product ion spectra obtained as a result of the product ion scan measurement (for example, Patent Literatures 1 and 2).